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Abstract: In principle, the technique of gene delivery involves taking complete or parts of genes that can code specific message and delivering them to selected cells in the body. Such a transfer of plasmid DNA into mammalian cells has posed major challenges for gene therapy. This study shows the encapsulation of a plasmid DNA in cross-linked polyvinylpyrrolidone (PVP) nanoparticles of size less than 100nm. This kind of encapsulation provides complete protection to the plasmid DNA from external DNase environment and generates the hope that the resulting formulation can be developed into a potential vector for effective gene delivery. In order to check this potentially, the reporter gene pSVβ-gal was encapsulated and in vitro transfection efficiency of this system was found to be nearly 80% compared to the commercially available transfection reagent PolyfectR. Further, in vivo biodistribution studies indicated that this system could be used safely for effective gene delivery. [Copyright &y& Elsevier]